Journal:Acta Cryst D:S2059798323006642
From Proteopedia
Atypical Homodimerisation Revealed by the Structure of (S)-Enantioselective Haloalkane Dehalogenase DmmarA from Mycobacterium marinumKarolina Snajdarova, Sérgio M. Marques, Jiri Damborsky, David Bednar, Martin Marek [1] Molecular Tour Haloalkane dehalogenases:
 Atomic-level knowledge of both the inner organization and supramolecular complexation of HLDs is thus crucial for our understanding of their catalytic and non-catalytic functions. Here, we determined crystallographic structures of an (S)-enantioselective haloalkane dehalogenase DmmarA from the waterborne pathogenic microbe Mycobacterium marinum at 1.6 Å and 1.85 Å resolutions.  Overall structure of DmmarA:
Chain A is displayed as a blue cartoon, and chain B as a light blue cartoon. Amino acids forming the catalytic pentad are visualized as green spheres. The L5 loop is colored purple. The structures show a canonical αβα-sandwich HLD fold with several unusual structural features. Mechanistically, the atypical composition of a proton-relay catalytic triad (aspartate-histidine-aspartate) and uncommon active site pocket expose molecular specificities of catalytic apparatus that exhibits rare (S)-enantiopreference. Active sites of DmmarA and Rhodobacteraceae bacterium UDC319 Haloalkane dehalogenase (HanR; 4brz):
Additionally, the structures reveal an as-yet-unseen mode of symmetric homodimerization, which is predominantly mediated through unusual L5-to-L5 loops interactions. (chain A is displayed as a blue cartoon, and chain B as a light blue cartoon; the L5 loop is colored purple). In the , interacting residues are shown as ball-and-sticks. Water molecules are shown as red spheres, bonds as white dashed lines. This homodimeric association in a solution is confirmed experimentally by data obtained from small-angle X-ray scattering. Utilizing the newly determined structures of DmmarA, molecular modelling techniques were employed to elucidate the underlying mechanism behind its uncommon enantioselectivity. The (S)-preference can be attributed to the presence of a distinct binding pocket and variances in the activation barrier of nucleophilic substitution. . Remember to drag the structures with the mouse to rotate them. . The loop is shown in purple, and the residues of the loop as purple ball-and-sticks. The rest of the enzyme is visualized in blue space-fill representation. L5 loop conformation types:
Diverse dimerization modes in the HLD family:
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